title: A functional role for osteopontin in experimental crescentic glomerulonephritis in the rat.
abstract: This study examined whether osteopontin (OPN), a molecule with monocyte chemotactic and adhesive activity, participates in macrophage-mediated renal disease, Accelerated anti-glomerular basement membrane glomerulonephritis was induced in groups of six rats. Animals were treated with a neutralizing anti-OPN or an irrelevant control antibody over days 0-7 (induction phase) or days 7-14 (established disease). Administration of the control antibody had no effect on the severity of the disease. In contrast, anti-OPN treatment significantly reduced glomerular injury (urinary protein excretion) and prevented a loss of renal function (creatinine clearance) during the induction of disease. This was accompanied by a significant reduction in renal macrophage and T-cell accumulation, T-cell activation, and histological injury (glomerular hypercellularity, segmental lesions, crescents, and tubulointerstitial lesions). An important finding was that anti-OPN treatment of established crescentic glomerulonephritis led to a significant reduction in glomerular injury and recovery of renal function in association with inhibition of macrophage and T-cell accumulation, T-cell activation, and histological damage. Anti-OPN treatment significantly inhibited the upregulation of OPN and its ligand CD44 but demonstrated no effect on upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in the kidney. Interestingly, anti-OPN treatment significantly reduced skin swelling and leukocyte infiltration in the delayed type hypersensitivity response. However, anti-OPN treatment had no effect on the humoral immune response. In summary, this study has demonstrated that OPN plays a functional role in macrophage and T-cell accumulation and renal damage in both the induction and progression of a rat model of crescentic glomerulonephritis. Thus, OPN may be of pathological importance in human glomerulonephritis and in cell-mediated immune diseases generally.
authors.affiliation: Department of Nephrology, First Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou, China.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Yu
authors.forename: D J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
authors.forename: W
authors.initials: W
authors.lastname: Mu
authors.forename: C M
authors.initials: CM
authors.lastname: Giachelli
authors.forename: R C
authors.initials: RC
authors.lastname: Atkins
authors.forename: R J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: H Y
authors.initials: HY
authors.lastname: Lan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006968:Hypersensitivity, Delayed; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007668:Kidney / Q000503:physiopathology; D007962:Leukocytes / Q000166:cytology; D008297:Male; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000276:immunology*; D012867:Skin / Q000276:immunology
chemical_list: D018960:Hyaluronan Receptors; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D018799:Intercellular Adhesion Molecule-1